TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8073	24442;24443;24444	chr2:178719173;178719172;178719171	chr2:179583900;179583899;179583898
N2AB	7756	23491;23492;23493	chr2:178719173;178719172;178719171	chr2:179583900;179583899;179583898
N2A	6829	20710;20711;20712	chr2:178719173;178719172;178719171	chr2:179583900;179583899;179583898
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-65
• Domain position: 89
• Structural Position: 175
• Q(SASA): 0.2927
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
T/N	None	None	0.175	N	0.305	0.106	0.345405024496	gnomAD-4.0.0	1.32035E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-05	0	3.66327E-05

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
T/A	0.0774	likely_benign	0.0799	benign	-0.8	Destabilizing	0.042	N	0.298	neutral	N	0.48441579	None	None	N
T/C	0.3751	ambiguous	0.3907	ambiguous	-0.546	Destabilizing	0.958	D	0.437	neutral	None	None	None	None	N
T/D	0.2704	likely_benign	0.284	benign	-0.486	Destabilizing	0.001	N	0.231	neutral	None	None	None	None	N
T/E	0.2093	likely_benign	0.2318	benign	-0.498	Destabilizing	0.055	N	0.437	neutral	None	None	None	None	N
T/F	0.1349	likely_benign	0.1512	benign	-0.95	Destabilizing	0.497	N	0.503	neutral	None	None	None	None	N
T/G	0.245	likely_benign	0.2512	benign	-1.039	Destabilizing	0.22	N	0.499	neutral	None	None	None	None	N
T/H	0.1379	likely_benign	0.1514	benign	-1.37	Destabilizing	0.667	D	0.488	neutral	None	None	None	None	N
T/I	0.103	likely_benign	0.11	benign	-0.258	Destabilizing	0.001	N	0.305	neutral	N	0.505835657	None	None	N
T/K	0.1248	likely_benign	0.1379	benign	-0.765	Destabilizing	0.055	N	0.447	neutral	None	None	None	None	N
T/L	0.0745	likely_benign	0.0781	benign	-0.258	Destabilizing	0.02	N	0.444	neutral	None	None	None	None	N
T/M	0.0741	likely_benign	0.079	benign	0.117	Stabilizing	0.497	N	0.459	neutral	None	None	None	None	N
T/N	0.092	likely_benign	0.0966	benign	-0.708	Destabilizing	0.175	N	0.305	neutral	N	0.502256635	None	None	N
T/P	0.3437	ambiguous	0.3297	benign	-0.407	Destabilizing	0.301	N	0.49	neutral	D	0.539946777	None	None	N
T/Q	0.1562	likely_benign	0.1706	benign	-0.95	Destabilizing	0.011	N	0.313	neutral	None	None	None	None	N
T/R	0.0947	likely_benign	0.0995	benign	-0.482	Destabilizing	0.001	N	0.308	neutral	None	None	None	None	N
T/S	0.0934	likely_benign	0.0985	benign	-0.957	Destabilizing	0.008	N	0.159	neutral	N	0.496618741	None	None	N
T/V	0.1029	likely_benign	0.1077	benign	-0.407	Destabilizing	0.004	N	0.119	neutral	None	None	None	None	N
T/W	0.3746	ambiguous	0.3964	ambiguous	-0.871	Destabilizing	0.958	D	0.509	neutral	None	None	None	None	N
T/Y	0.1623	likely_benign	0.1796	benign	-0.632	Destabilizing	0.667	D	0.497	neutral	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.